Details for: FCRL5

Gene ID: 83416

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: FCRL5

Ensembl ID: ENSG00000143297

Description: Fc receptor like 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • mature B cell CL0000785
    CSI 19.7
    rCSI 17.12%
    PRS 96.15
  • transitional stage B cell CL0000818
    CSI 10.21
    rCSI 33.43%
    PRS 97.45
  • plasma cell CL0000786
    CSI 7.6
    rCSI 9.96%
    PRS 95.32
  • unswitched memory B cell CL0000970
    CSI 7.5
    rCSI 6.31%
    PRS 97.43
  • plasmablast CL0000980
    CSI 5.06
    rCSI 3.98%
    PRS 93.19
  • IgG plasma cell CL0000985
    CSI 4.17
    rCSI 4.99%
    PRS 94.43
  • IgA plasma cell CL0000987
    CSI 4.05
    rCSI 4.14%
    PRS 92.63
  • immature B cell CL0000816
    CSI 3.85
    rCSI 2.86%
    PRS 96.19
  • basal cell of epidermis CL0002187
    CSI 3.54
    rCSI 6.27%
    PRS 63.24
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.37
    rCSI 2.35%
    PRS 93.95
  • germinal center B cell CL0000844
    CSI 2.46
    rCSI 7.33%
    PRS 94.17
  • class switched memory B cell CL0000972
    CSI 2.37
    rCSI 1.77%
    PRS 96.58
  • suprabasal keratinocyte CL4033013
    CSI 1.56
    rCSI 2.55%
    PRS 63.18
  • IgM plasma cell CL0000986
    CSI 1.35
    rCSI 6.06%
    PRS 96.9

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [FCRL5](/details-gene/83416) (Fc Receptor Like 5) is a type I transmembrane protein and a member of the immunoglobulin receptor superfamily. It is predominantly expressed on cells of the B-lymphocyte lineage, where it functions as a co-receptor involved in modulating B-cell activation and immune responses. The gene is located on chromosome 1q23.1, a region frequently associated with abnormalities in B-cell malignancies. Its high expression on mature and memory B cells, coupled with its role in signaling, positions [FCRL5](/details-gene/83416) as a key regulator of humoral immunity and a potential biomarker or therapeutic target in hematological cancers. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [FCRL5](/details-gene/83416) highlights its central role in the B-cell compartment of the immune system. The gene shows its highest significance in [mature B cell](/details-cell/CL0000785) (CSI: 19.70), indicating it is a defining marker for this population. Its expression is also highly significant across various stages of B-cell development and differentiation, including [transitional stage B cell](/details-cell/CL0000818), [plasma cell](/details-cell/CL0000786), [unswitched memory B cell](/details-cell/CL0000970), and [plasmablast](/details-cell/CL0000980). This consistent expression pattern across the B-cell lineage has been documented in several studies identifying it as part of a family of receptors preferentially expressed in B cells ([Link](https://doi.org/10.1073/pnas.171308498); [Link](https://doi.org/10.1182/blood.v99.8.2662)). Intriguingly, [FCRL5](/details-gene/83416) also shows a notable, albeit lower, expression signature in non-hematopoietic cells, specifically [basal cell of epidermis](/details-cell/CL0002187) (CSI: 3.54) and [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 1.56). This suggests a potential secondary function for the protein in the context of skin biology, possibly related to epithelial barrier function or innate immune surveillance. ## Pathways and Molecular Function The functional annotations for [FCRL5](/details-gene/83416) are highly consistent with its observed expression in B lymphocytes. Its localization to the [cell surface](/details-cell/GO:0009986) and [external side of plasma membrane](/details-cell/GO:0009897) enables its function in [transmembrane signaling receptor activity](/details-cell/GO:0004888). **Biological Process:** [FCRL5](/details-gene/83416) is annotated to play a role in the [immune response](/details-cell/GO:0006955), particularly in the [cell surface receptor signaling pathway](/details-cell/GO:0007166) and, more specifically, [B cell activation](/details-cell/GO:0042113). This is strongly supported by research demonstrating that [FCRL5](/details-gene/83416) can form a receptor complex with CD21 to potentiate B-cell activation signals ([Link](https://doi.org/10.1093/intimm/dxy052)). **Molecular Function:** At the molecular level, it exhibits [coreceptor activity](/details-cell/GO:0015026) and [protein binding](/details-cell/GO:0005515) capabilities, which are essential for its role in integrating signals at the B-cell surface. ## Research Directions The specific expression of [FCRL5](/details-gene/83416) on B cells, combined with its chromosomal location and reported dysregulation in cancers like B-chronic lymphocytic leukemia ([Link](https://doi.org/10.1093/intimm/dxl069)), positions it as a gene of significant clinical interest. **Proposed Hypotheses:** 1. Given its function as an activating co-receptor, aberrant signaling or overexpression of [FCRL5](/details-gene/83416) on malignant B cells may contribute to lymphomagenesis by providing pro-survival signals or lowering the threshold for B-cell receptor activation, thereby promoting uncontrolled proliferation. 2. The unexpected expression of [FCRL5](/details-gene/83416) in epidermal keratinocytes suggests a novel, non-canonical role in cutaneous immunity. It may function as a pattern recognition receptor or a sensor for epithelial damage, contributing to the initiation of local inflammatory responses in the skin. **Experimental Approach:** To test the hypothesis regarding its role in skin immunity, a compelling experiment would be to use an in vitro model of human keratinocytes. CRISPR-Cas9 could be used to knock out [FCRL5](/details-gene/83416) in a keratinocyte cell line (e.g., HaCaT) or primary human epidermal keratinocytes. These knockout cells, along with wild-type controls, would then be challenged with bacterial ligands (e.g., LPS, LTA) or pro-inflammatory stimuli (e.g., TNF-alpha). The cellular response could be comprehensively profiled using RNA-seq to identify [FCRL5](/details-gene/83416)-dependent gene expression networks, and cytokine/chemokine secretion could be quantified by multiplex ELISA to determine its impact on the inflammatory secretome of the epidermis. **Therapeutic Potential:** The high specificity of [FCRL5](/details-gene/83416) expression on the B-cell surface makes it a highly attractive target for therapeutic intervention in B-cell malignancies. Its presence on the plasma membrane is ideal for antibody-based therapies. Therefore, [FCRL5](/details-gene/83416) represents a promising target for the development of antibody-drug conjugates (ADCs) or Chimeric Antigen Receptor (CAR)-T cells. Such strategies would aim to selectively eliminate cancerous B cells while sparing other tissues, suggesting that targeted **inhibition** or cell killing, rather than activation, would be the therapeutic goal.

Genular Protein ID: 1112527922

Symbol: FCRL5_HUMAN

Name: Fc receptor-like protein 5

UniProtKB Accession Codes:

Q96RD9 A0N0M2 B7WNT9 B7WP94 Q495Q2 Q495Q4 Q5VYK9 Q6UY46

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 3 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 RefSeq 2 SMART 2 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11453668

Title: BXMAS1 identifies a cluster of homologous genes differentially expressed in B cells.

PubMed ID: 11453668

DOI: 10.1006/bbrc.2001.5231

PubMed ID: 11290337

Title: IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy.

PubMed ID: 11290337

DOI: 10.1016/s1074-7613(01)00109-1

PubMed ID: 11493702

Title: Identification of a family of Fc receptor homologs with preferential B cell expression.

PubMed ID: 11493702

DOI: 10.1073/pnas.171308498

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11929751

Title: IRTAs: a new family of immunoglobulin-like receptors differentially expressed in B cells.

PubMed ID: 11929751

DOI: 10.1182/blood.v99.8.2662

PubMed ID: 16849395

Title: Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia.

PubMed ID: 16849395

DOI: 10.1093/intimm/dxl069

PubMed ID: 30107486

Title: CD21 and FCRL5 form a receptor complex with robust B-cell activating capacity.

PubMed ID: 30107486

DOI: 10.1093/intimm/dxy052

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 977
  • Mass: 106437
  • Checksum: 9545DA1B6A164FDD
  • Sequence:
    • MLLWVILLVL APVSGQFART PRPIIFLQPP WTTVFQGERV TLTCKGFRFY SPQKTKWYHR 
YLGKEILRET PDNILEVQES GEYRCQAQGS PLSSPVHLDF SSASLILQAP LSVFEGDSVV 
LRCRAKAEVT LNNTIYKNDN VLAFLNKRTD FHIPHACLKD NGAYRCTGYK ESCCPVSSNT 
VKIQVQEPFT RPVLRASSFQ PISGNPVTLT CETQLSLERS DVPLRFRFFR DDQTLGLGWS 
LSPNFQITAM WSKDSGFYWC KAATMPYSVI SDSPRSWIQV QIPASHPVLT LSPEKALNFE 
GTKVTLHCET QEDSLRTLYR FYHEGVPLRH KSVRCERGAS ISFSLTTENS GNYYCTADNG 
LGAKPSKAVS LSVTVPVSHP VLNLSSPEDL IFEGAKVTLH CEAQRGSLPI LYQFHHEGAA 
LERRSANSAG GVAISFSLTA EHSGNYYCTA DNGFGPQRSK AVSLSVTVPV SHPVLTLSSA 
EALTFEGATV TLHCEVQRGS PQILYQFYHE DMPLWSSSTP SVGRVSFSFS LTEGHSGNYY 
CTADNGFGPQ RSEVVSLFVT VPVSRPILTL RVPRAQAVVG DLLELHCEAP RGSPPILYWF 
YHEDVTLGSS SAPSGGEASF NLSLTAEHSG NYSCEANNGL VAQHSDTISL SVIVPVSRPI 
LTFRAPRAQA VVGDLLELHC EALRGSSPIL YWFYHEDVTL GKISAPSGGG ASFNLSLTTE 
HSGIYSCEAD NGLEAQRSEM VTLKVAVPVS RPVLTLRAPG THAAVGDLLE LHCEALRGSP 
LILYRFFHED VTLGNRSSPS GGASLNLSLT AEHSGNYSCE ADNGLGAQRS ETVTLYITGL 
TANRSGPFAT GVAGGLLSIA GLAAGALLLY CWLSRKAGRK PASDPARSPS DSDSQEPTYH 
NVPAWEELQP VYTNANPRGE NVVYSEVRII QEKKKHAVAS DPRHLRNKGS PIIYSEVKVA 
STPVSGSLFL ASSAPHR